Lysosomal alpha-mannosidase and alpha-mannosidosis

Lysosomal alpha-mannosidase is ubiquitous in human tissues where is expressed in two major forms, A and B that are the product of a single gene located on chromosome 19. Mutations in the gene encoding for alpha-mannosidase cause alpha- mannosidosis, an autosomal recessive disease resulting in the accumulation of unprocessed mannose-containing oligosaccharide material. This rare disease has an estimated incidence of 1/500.000 live births and is clinically divided into three subgroups. Today the most promising therapy for this disease is the enzyme replacement therapy. To develop this strategy a mouse model for alpha-mannosidosis has been generated and a recombinant human alpha-mannosidase has been produced from Chinese Hamster Ovary cells. Interestingly, it has been shown that the recombinant enzyme, used in high dose, can cross the blood brain barrier. The recombinant enzyme has been tested in the first randomized study investigating the efficacy of the enzyme replacement therapy in patients with alpha-mannosidosis. This review contains the scientific progresses on lysosomal alpha-mannosidase from the cloning to the beginning of the therapy.